Nitric Oxide Donors in Cardiovascular Disease

Clinical Cardiovascular Applications of NO Donor Therapy - Past and Present 

Murrell, who reported in 1879 that a one percent solution of the drug administered sublingually relieved angina and prevented attacks thereafter [2], 

Although control of the symptoms of acute angina pectoris had become possible with amyl nitrite and NTG, their short duration of action did not allow prophylactic 

This hypothesis clearly contradicted a large body of clinical evidence that nitrates were effective. Some years later, using more sensitive and reliable analytical methods, this interpretation was shown to be incorrect, and the clinical utility of long-acting, oral organic nitrate derivatives affirmed. In 1967, one of the pharmacodynamically active metabolites of ISDN, IS-5N, was shown to be formed in vivo, and shortly thereafter it was introduced as a novel long-acting NO donor with improved bioavailability. 

The pharmacological mechanisms of action of NO donors that contribute to their benefit in coronary artery disease, congestive heart failure, and hypertension are listed in Table 11.1. These actions can be grouped into five categories vasodilation, decrease in myocardial oxygen consumption, improvement in hemodynamic performance, 

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In contrast, drugs that release endogenous nitric oxide and donors of the molecule were in use long before nitric oxide was discovered and continue to be very important in clinical medicine. The cardiovascular applications of nitroprusside (Chapter 11) and the nitrates and nitrites (Chapter 12) have been discussed. The treatments of preeclampsia and of pulmonary hypertension and acute respiratory distress syndrome are currently under clinical investigation. Early results from the pulmonary disease studies appear promising, and one preparation of nitric oxide gas (INOmax) has been approved for use in neonates with hypoxic respiratory failure. 

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